Hollis T M, Gardner T W, Vergis G J, Kirbo B J, Butler C, Dull R O, Campos M J, Enea N A
Department of Biology, Pennsylvania State University, University Park 16802.
J Diabet Complications. 1988 Jan-Mar;2(1):47-9. doi: 10.1016/0891-6632(88)90029-3.
Retinal and other tissue histamine synthesis is increased in experimental diabetes; histamine infusion causes blood-ocular barrier breakdown in nondiabetic rats. We have examined the hypothesis that antihistamines prevent blood-ocular barrier breakdown in streptozotocin diabetes using male Sprague-Dawley rats held 28 days. During the last 7 days they were divided into these treatment groups: control (C), untreated diabetic (D), diabetic rats receiving diphenhydramine-HCl (B), diabetic rats receiving ranitidine (R) and diabetic rats receiving diphenhydramine and ranitidine (BR). Vitreous albumin content was measured 6 hr following fluorescein isothiocyanate bovine serum albumin (FITCBSA) injection. Data show that D had a 98.3% increase in vitreous body FITCBSA over C (p less than 0.05) while B and R showed respective decreases of 34.9% and 51.4% compared to D, R being significantly lower than D (p less than 0.05). BR showed a decrease of 71% (p less than 0.05) compared to D, and R and BR groups were not significantly different from C (p less than 0.05). Leakage into the vitreous was from the retina, not the ciliary body. These data indicate that 1) experimental diabetes results in elevated blood-ocular barrier permeability, which can be reversed by diphenhydramine-HCl and ranitidine; and 2) histamine H1- and H2-receptor activation and interaction by altered endogenous histamine metabolism may mediate blood-ocular barrier breakdown, implicating a pathogenic role of histamine in diabetic retinopathy.
实验性糖尿病会使视网膜及其他组织中的组胺合成增加；组胺输注会导致非糖尿病大鼠的血眼屏障破坏。我们使用饲养28天的雄性Sprague-Dawley大鼠检验了抗组胺药可预防链脲佐菌素诱导的糖尿病中血眼屏障破坏这一假说。在最后7天，它们被分为以下治疗组：对照组（C）、未治疗的糖尿病组（D）、接受盐酸苯海拉明的糖尿病大鼠组（B）、接受雷尼替丁的糖尿病大鼠组（R）以及接受苯海拉明和雷尼替丁的糖尿病大鼠组（BR）。在注射异硫氰酸荧光素标记的牛血清白蛋白（FITCBSA）6小时后测量玻璃体白蛋白含量。数据显示，与C组相比，D组玻璃体中FITCBSA增加了98.3%（p<0.05），而与D组相比，B组和R组分别下降了34.9%和51.4%，R组显著低于D组（p<0.05）。与D组相比，BR组下降了71%（p<0.05），且R组和BR组与C组无显著差异（p<0.05）。玻璃体渗漏来自视网膜，而非睫状体。这些数据表明：1）实验性糖尿病导致血眼屏障通透性升高，盐酸苯海拉明和雷尼替丁可使其逆转；2）组胺H1和H2受体激活以及内源性组胺代谢改变所导致的相互作用可能介导血眼屏障破坏，这意味着组胺在糖尿病视网膜病变中具有致病作用。
